Preparation of N-Aryl Amides by Epimerization-Free Umpolung Amide Synthesis.
Preparation of N-Aryl Amides by Epimerization-Free Umpolung Amide Synthesis.
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DOI：
10.1021/jacs.2c05986
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发表时间：
2022-09-21
影响因子：
15
通讯作者：
Johnston, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Crocker, Michael S.;Deng, Zihang;Johnston, Jeffrey N.
Amide synthesis is one of the most widely practiced chemical reactions, owing to its use in drug development and peptide synthesis. Despite the importance of these applications, the attendant effort to eliminate waste associated with these protocols has met with limited success, and pernicious α-epimerization is most often minimized but not eliminated when targeting challenging amides (e.g. N-aryl amides). This effort has focused on what is essentially a single paradigm in amide formation wherein an electrophilic acyl donor reacts with a nucleophilic amine. Umpolung Amide Synthesis (UmAS) emerged from α-halo nitroalkane reactions with amines and has since been developed into a method for the synthesis of enantiopure amides using entirely catalytic, enantioselective synthesis. However, its inability to forge N-aryl amides has been a longstanding problem, one limiting its application more broadly in drug development where α-chiral N-aryl amides are increasingly common. We report here the reaction of α-fluoronitroalkanes and N-aryl hydroxyl amines for the direct synthesis of N-aryl amides using a simple Brønsted base as the promoter. No other activating agents are required, and experiments guided by mechanistic hypotheses outline a mechanism based on the UmAS paradigm and confirm that the N-aryl amide, not the N-aryl hydroxamic acid, is the direct product. Ultimately, select chiral α-amino-N-aryl amides were prepared with complete conservation of enantioenrichment, in contrast to a parallel demonstration of their ability to epimerize using the conventional amide synthesis alternative.
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DOI：
10.15227/orgsyn.093.0088
发表时间：
2016
期刊：
Organic syntheses; an annual publication of satisfactory methods for the preparation of organic chemicals
影响因子：
--
作者：
Lim VT;Tsukanov SV;Stephens AB;Johnston JN
通讯作者：
Johnston JN
影响因子：
3.6
作者：
Chen, Yu-Feng;Chen, Jing;Chuang, Gary Jing
通讯作者：
Chuang, Gary Jing
影响因子：
3.6
作者：
DIJKSTRA, G;KRUIZINGA, WH;KELLOGG, RM
通讯作者：
KELLOGG, RM
影响因子：
23.5
作者：
Crocker, Michael S.;Foy, Hayden;Johnston, Jeffrey N.
通讯作者：
Johnston, Jeffrey N.
影响因子：
5.2
作者：
Fisher, David J.;Shaum, James B.;de Alaniz, Javier Read
通讯作者：
de Alaniz, Javier Read